Diet-induced obesity typically results from a combination of excessive food energy intake, favored by an evolutionary remain associating energy-dense food with greater taste, lack of physical activity and genetic susceptibility. Obesity is at the origin of a wide range of diseases such as cardiovascular disorders, type 2 diabetes, obstructive sleep apnea, osteoarthritis, asthma and certain types of cancer and has become a leading preventable cause of death with dramatically increasing prevalence, affecting up to 1.5 billion people in industrialized and developing countries. A sustainable change in lifestyle including dieting and physical exercise is the pillar for the treatment of obesity that can be complemented by gastric balloon and bariatric surgery to assist weight loss and by taking anti-obesity drugs to reduce appetite or fat absorption. However, dieting often shows limited success, surgery is associated with significant risks, and only some anti-obesity drugs with modest efficacy remain on the market after many have been withdrawn because of side effects and few have entered clinical trials since. The amylin analogue pramlintide has recently been licensed as injection-based adjunctive type 2 diabetes therapy as it reduces adsorption of glucose and other nutrients such as fat by slowing gastric emptying, promotes satiety via GLP-1-independent hypothalamic receptors and inhibits inappropriate secretion of glucagon (Younk, L. M. et al., Expert Opin Pharmacother 12, 1439-1451 (2011)). However, precise injection-based dosing at mealtime remains challenging due the short half-life of the synthetic peptide hormone.
Synthetic biology-inspired designer networks that coordinate caloric intake to satiety responses could control dietary energy homeostasis and may provide a new strategy for the treatment of obesity.